Repression of a matrix metalloprotease gene by E1A correlates with its ability to bind to cell type-specific transcription factor AP-2

Kumaravel Somasundaram, Gopalswamy Jayaraman, Trevor Williams, Elizabeth Moran, Steven Frisch, Bayar Thimmapaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Adenovirus E1A 243-amino acid protein can repress a variety of enhancer- linked viral and cellular promoters. This repression is presumed to be mediated by its interaction with and sequestration of p300, a transcriptional coactivator. Type IV 72-kDa collagenase is one of the matrix metalloproteases that has been implicated in differentiation, development, angiogenesis, and tumor metastasis. We show here that the cell type-specific transcription factor AP-2 is an important transcription factor for the activation of the type IV 72-kDa collagenase promoter and that adenovirus E1A 243-amino acid protein represses this promoter by targeting AP-2. Glutathione S-transferase- affinity chromatography studies show that the E1A protein interacts with the DNA binding/dimerization region of AP-2 and that the N-terminal amino acids of E1A protein are required for this interaction. Further, E1A deletion mutants which do not bind to p300 can repress this collagenase promoter as efficiently as the wild-type E1A protein. Because the AP-2 element is present in a variety of viral and cellular enhancers which are repressed by E1A, these studies suggest that EtA protein can repress cellular and viral promoter/enhancers by forming a complex with cellular transcription factors and that this repression mechanism may be independent of its interaction with p300.

Original languageEnglish (US)
Pages (from-to)3088-3093
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number7
DOIs
StatePublished - Apr 2 1996

ASJC Scopus subject areas

  • General

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